American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 2023
In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk and Lung Cancer Incidence and Mortality in Adulthood.
Rationale: The individual effects of early-life tobacco smoke exposure and its interactions with genetic factors on lung cancer in adulthood remain unclear. Objectives: To investigate the associations of early-life tobacco exposures as well as their interactions with polygenic risk scores (PRSs) with lung cancer incidence and mortality. Methods: A total of 432,831 participants from the UK Biobank study were included. ⋯ Participants with high PRSs and in utero tobacco exposure (versus low PRSs participants without in utero exposure) had an HR of 2.35 for lung cancer incidence (95% CI, 1.97-2.80, Pinteraction = 0.089) and 2.43 for mortality (95% CI, 2.05-2.88, Pinteraction = 0.032). High PRSs with smoking initiation in childhood (versus never-smokers with low PRSs) had HRs of 18.71 for incidence (95% CI, 14.21-24.63, Pinteraction = 0.004) and 19.74 for mortality (95% CI, 14.98-26.01, Pinteraction = 0.033). Conclusions: In utero and childhood/adolescence exposure to tobacco smoke and its interaction with genetic factors may substantially increase the risks of lung cancer incidence and mortality in adulthood.
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Am. J. Respir. Crit. Care Med. · Jan 2023
Forgiveness Is the Attribute of the Strong: Nonadherence and Regimen-Shortening in Drug-Sensitive TB.
Rationale: "Forgiveness" charts the ability of a drug or regimen to withstand nonadherence without negative clinical consequences. Objectives: We aimed to determine the influence of regimen length, regimen drugs, and dosing, and when during treatment nonadherence occurs on the forgiveness of antituberculosis regimens. Methods: Using data from three randomized controlled trials comparing experimental 4-month regimens for drug-sensitive tuberculosis with the standard 6-month regimen, we used generalized linear models to examine how the risk of a negative composite outcome changed as dose-taking decreased. ⋯ We found evidence of mediation by continuation phase dose-taking on the intensive phase dose-taking and negative composite outcome relationship. Conclusions: With the current appetite for, and progress toward, shorter drug-sensitive tuberculosis regimens worldwide, we offer reassurance that shorter regimens are not necessarily less forgiving of nonadherence. Given the importance of continuation phase adherence, patient support during this period should not be neglected.